1. Field of the Invention
The present invention relates to an anti-tenascin C peptide aptamer and its uses.
2. Background of Technique
In addition to genetic mutations in cancer cells themselves, tumorigenesis is also accompanied by changes in the surrounding stroma and extracellular matrix (ECM). Interactions between tumor and stromal cells contribute to tumor formation and progression, but the ECM proteins involved remain to be identified. Tenascin C is an adhesion modulatory ECM protein that is expressed during development, but not in normal adult tissues (1, 2). It is mostly found in tumor-specific microenvironments and its high level expression appears to play a role in tumor formation and progression (3, 4).
Tenascin proteins (C, X, R and W) are large glycoproteins that form multimeric complexes and may contribute to pathological states in which tissue remodeling processes are involved (1, 2, 4). For example, it is likely that tenascin C stimulates diverse signaling pathways leading to cell proliferation, invasion and tumor formation (5).
The prominent expression of tenascin C in many solid tumors provides an outstanding diagnostic and therapeutic target for tumor site detection and treatment in vivo. Especially, a large isoform of tenascin C is generated by alternative splicing of mRNA and its protein expression has been shown to be associated with tumor progression (6-8). Since tenascin C is a potential biomarker for the diagnosis and prognosis of many cancers (9), anti-tenascin C antibodies are effective in tumor targeting and a radiolabeled monoclonal antibody is in clinical trial (10-12). In addition, RNA aptamers have also been generated to be used as targeting and imaging tools (13, 14).
Throughout this application, various publications and patents are referred and citations are provided in parentheses. The disclosures of these publications and patents in their entities are hereby incorporated by references into this application in order to fully describe this invention and the state of the art to which this invention pertains.